The behavioral, biochemical, and histological effects of tissue implants in rodent and primate models of Parkinsonism is being studied. Fetal dopaminergic grafts have lead to almost complete functional recovery in the monkeys, with lesser improvement seen after non-dopaminergic fetal grafts, adrenal grafts, or operative trauma alone. In all the animals studied thus far, there has been sprouting of tyrosine hydroxylase-positive fibers into the denervated caudate, which may account for part of the recovery seen (especially in animals where no dopaminergic tissue survives). We are actively investigating the role of dopamine secretion by implanted cells and fiber sprouting in the behavioral improvement. Another important aspect of the project is to examine technical questions associated with implantation. The use of stereotactic cell deposition has been carefully studied and a reliable method in rat and primate brain worked out. The immunological factors involved in allotransplantation are under study, including HLA expression and peripheral evidence of rejection occurring within the brain. PET and glucose utilization studies after implantation are being correlated with functional changes. The use of an in vivo dialysis catheter is being explored to assess dopamine metabolism. Finally, we are studying dopaminergic tissues for potential clinical use, including human fetal mesencephalon.